Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT51SVLH)

• DOT Name: Protein THEM6 (THEM6)
• Synonyms: Mesenchymal stem cell protein DSCD75; Thioesterase superfamily member 6
• Gene Name: THEM6
• Related Disease:
  Colorectal carcinoma
  Liver cirrhosis
• UniProt ID: THEM6_HUMAN
• Pfam ID: PF13279
• Sequence:
  MLGLLVALLALGLAVFALLDVWYLVRLPCAVLRARLLQPRVRDLLAEQRFPGRVLPSDLD
  LLLHMNNARYLREADFARVAHLTRCGVLGALRELRAHTVLAASCARHRRSLRLLEPFEVR
  TRLLGWDDRAFYLEARFVSLRDGFVCALLRFRQHLLGTSPERVVQHLCQRRVEPPELPAD
  LQHWISYNEASSQLLRMESGLSDVTKDQ

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[1]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[2]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Protein THEM6 (THEM6).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Protein THEM6 (THEM6).	[11]

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein THEM6 (THEM6).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein THEM6 (THEM6).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein THEM6 (THEM6).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Protein THEM6 (THEM6).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Protein THEM6 (THEM6).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein THEM6 (THEM6).	[9]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein THEM6 (THEM6).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein THEM6 (THEM6).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein THEM6 (THEM6).	[13]

References

• [1] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysis and subsequent verification using selected reaction monitoring (SRM) and tissue microarray (TMA) analysis.Mol Cell Proteomics. 2014 Jun;13(6):1471-84. doi: 10.1074/mcp.M113.037093. Epub 2014 Mar 31.
• [2] Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis.Ther Clin Risk Manag. 2017 Jun 22;13:733-738. doi: 10.2147/TCRM.S133983. eCollection 2017.
• [3] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [4] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [11] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [12] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [13] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.